Compressing a Non‐Planar Aromatic Heterocyclic [7]Helicene to a Planar Hetero[8]Circulene

Abstract

This work describes as ynthetica pproachw here an on-planar aromatic heterocyclic [7]helicene is compressedt oy ield ah etero[8]circulene containing an inner antiaromatic cyclooctatetraene (COT) core. This [8]circulene consists of four benzene rings and four heterocyclic rings, and it is the first heterocyclic[ 8]circulenec ontaining three differenth eteroatoms. The synthetic pathway proceeds via at he flattened dehydro-hetero[7]helicene, which is partially ah elicene and partially ac irculene:i ti s non-planar and helically chiral as helicenes, and contains a COT motif like [8]circulenes. The antiaromaticity of the COT core is confirmed by nucleusi ndependent chemical shift (NICS) calculations. The planarizationf rom ah elically p-conjugated[ 7]helicene to af ully planar heterocyclic [8]circulene significantly alterst he spectroscopicp roperties of the molecules.P ost-functionalization of the [7]helicenes and the [8]circulenes by oxygenation of the thiophene rings to the corresponding thiophene-sulfones allows an almost complete fluorescence emission coverage of the visible region of the opticals pectrum (400-700 nm).

Triggering G‐Quadruplex Conformation Switching with [7]Helicenes

“…[27] The diazathia [7]helicene motif has been reported to racemise readily at room temperature. [32] The new peak at 327 nm induced by L2 in the VTCD experiment with h-telo in Na + has am elting temperature of 14.2 8C. We consider this av alid estimation for the helicene racemisationb arrier, as the interaction between DNA and helicene ligand L2 is non-stabilising.…”

“…For this study, we use two hetero[7]helicene ligands: L1 and L2 . The helicene ligands obey many of the criteria described above (aromatic, hydrophobic and positively charged ammonium groups), but in contrast to previously studied ligands, the P ‐ and M ‐enantiomers of these helicene ligands interconvert rapidly at room temperature, [28, 31, 32] and consequently both of the two enantiomers are readily available for selective recognition of the G‐quadruplexes. We have found that these helicene ligands stabilise parallel k‐ras G‐quadruplexes and convert polymorphic h‐telo structures into conformations with increased parallel character.…”

“…[28,29] Typically,t he P-enantiomers show positive peaks in circulard ichroism (CD) spectroscopy, whereas M-enantiomers display negative peaks. [30] For [n]helicenes, the size of the racemisation barrierd epends on substituents in the bay region and the number and type of aromatic rings, n. [28] For this study,w eu se two hetero [7]helicene ligands: L1 and L2.T he helicene ligands obey many of the criteria described above (aromatic,h ydrophobic and positivelyc harged ammonium groups), but in contrast to previously studied ligands, the P-a nd M-enantiomers of these helicene ligandsi nterconvert rapidly at room temperature, [28,31,32] and consequently both of the two enantiomers are readily available for selective recognition of the G-quadruplexes. We have found that these helicene ligandss tabilise parallel k-ras G-quadruplexes and convert polymorphic h-telo structures into conformationsw ith increasedp arallel character.…”

“…The [7]helicene ligands L1 and L2 were prepared as racemates from our previously reported diazathia [7]helicene 1, [32] as shown in Scheme 1. Helicene 1 was alkylated using 1,4-dibromobutane to give 2,w hich, upon treatment with trimethyl-amine, quantitatively yielded the ammonium-functionalised helicene ligand L1.T oi nvestigate the effect of additional Hbond acceptors, in the form of as ulfone, L2 was synthesised in high yield, by oxidation of thiophene 2 to 3 using m-CPBA, prior to treatment with trimethylamine.…”

“…The [7]helicene ligands L1 and L2 were prepared as racemates from our previously reported diazathia[7]helicene 1 , [32] as shown in Scheme 1. Helicene 1 was alkylated using 1,4‐dibromobutane to give 2 , which, upon treatment with trimethylamine, quantitatively yielded the ammonium‐functionalised helicene ligand L1 .…”